Secondhand tobacco smoke and risk of atrial fibrillation: An observational epidemiologic and gene-environment interaction analysis

Tae-Min Rhee; Kyung-Yeon Lee; JungMin Choi; Hyo-Jeong Ahn; So-Ryoung Lee; Eue-Keun Choi; Seil Oh; Gregory Y H Lip

doi:10.1016/j.hrthm.2025.08.021

Secondhand tobacco smoke and risk of atrial fibrillation: An observational epidemiologic and gene-environment interaction analysis

Heart Rhythm. 2025 Aug 19:S1547-5271(25)02763-8. doi: 10.1016/j.hrthm.2025.08.021. Online ahead of print.

Authors

Tae-Min Rhee¹, Kyung-Yeon Lee², JungMin Choi³, Hyo-Jeong Ahn⁴, So-Ryoung Lee⁴, Eue-Keun Choi⁵, Seil Oh⁴, Gregory Y H Lip⁶

Affiliations

¹ Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea; Department of Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea.
² Department of Internal Medicine, Korea University Medicine Guro Hospital, Seoul, Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
³ Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
⁴ Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
⁵ Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: choiek17@snu.ac.kr.
⁶ Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Chest and Heart Hospital, Liverpool, United Kingdom; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.

PMID: 40840573
DOI: 10.1016/j.hrthm.2025.08.021

Abstract

Background: The relationship between secondhand tobacco smoke (SHS) and the risk of incident atrial fibrillation (AF) remains controversial.

Objective: This study aimed to evaluate the long-term risk of AF associated with SHS exposure and assess potential gene-environment interactions using extensive population-based data.

Methods: We performed a nationwide population-based cohort study using the UK Biobank database. Participants were categorized into SHS-exposure and nonexposure groups. The primary outcome was the risk of incident AF. We also evaluated the synergistic effect of SHS exposure and the polygenic risk score of AF.

Results: During a median follow-up of 12.5 years, AF occurred in 23,471 (5.9%). The SHS-exposure group (median exposure 0.5 [0.5-1.5] h/wk) was younger and predominantly male. The risk of AF was significantly higher in the SHS-exposure group (multivariable-adjusted hazard ratio 1.06; 95% confidence interval 1.02-1.09; P = .002) than the nonexposure group, suggesting a dose-dependent manner (adjusted hazard ratio of the severe SHS-exposure group 1.11; 1.04-1.18; P = .001). The risk of AF was higher in the SHS-exposure group regardless of the exposure location (home, outside, or workplace). When SHS exposure was combined with the high genetic risk of AF, a significant additive interaction was observed on the risk of AF (synergy index of SHS exposure with the third tertile of AF polygenic risk score 1.13; 1.05-1.21; P = .024).

Conclusion: Exposure to SHS is a significant predictor of an increased risk of AF, with a synergistic effect when combined with genetic predisposition. Minimizing SHS exposure, especially in individuals with a heightened genetic susceptibility to AF, may potentially reduce the future risk of AF.

Keywords: Atrial fibrillation; Gene-environment interaction; Genome-wide association study; Polygenic risk score; Secondhand smoke.